The Cold Spring Harbor Laboratory proposes to continue the course entitled "X-Ray Methods in Structural Biology" (formerly "Macromolecular Crystallography"), to be held in the Fall of 2006-2010. This intensive laboratory/computational 16-day course focuses on the major X-ray crystallographic techniques used to determine the three-dimensional structures of macromolecules. The course provides the opportunity for research workers in different areas of cancer biology and biochemistry to become familiar with the techniques and principles of macromolecular crystallography. It is designed for scientists with a working knowledge of protein structure and function, but who are new to macromolecular crystallography. Topics covered included crystallization (proteins, nucleic acids and complexes), crystal characterization, X-ray sources and optics, crystal freezing, data collection, data reduction, multi-wavelength anomalous diffraction, multiple isomorphous replacement, phase determination, solvent flattening, molecular replacement, non- crystallographic symmetry averaging, electron density map interpretation, structure refinement, structure validation, and structure presentation using molecular graphics. The faculty is chosen on the basis of their contributions to and knowledge of the areas covered in the course. The faculty is supplemented by a series of invited speakers who present current research in their field of expertise that illustrate the principles that are taught in the course. Participants learn through extensive hands-on experiments where they crystallize and determine a protein structure, along with lectures and informal discussions on the theory behind the techniques from world leaders in methods development. The course day starts in the morning and runs throughout the day until late at night. There is also a trip to the National Synchrotron Light Source facility at Brookhaven National Laboratory. Applications are open to a wide range of students including advanced graduate students, medical students, postdoctoral fellows, faculty at universities and medical schools, as well as Ph.D. and M.D. scientists from industry. The course is designed to allow students to learn techniques that can be immediately incorporated into their own research. This enables the training of new researchers who can not only solve structures relevant to cancer, e.g. oncogenes and tumor suppressor genes, but also contribute to rational drug design.